The major histocompatibility complex (MHC) Class I antigens are expressed on virtually all types of vertebrate cells examined. These highly polymorphic transmembrane glycoproteins have a 45 kD heavy chain consisting of a short cytoplasmic C-terminal tail, a transmembrane region, and an extracellular N-terminal sequence which encompasses three domains (.alpha..sub.1, .alpha..sub.2, and .alpha..sub.3). .alpha..sub.1 - and .alpha..sub.2 -domains carry all the immunological polymorphism, while the membrane-proximal .alpha..sub.3 domain is non-covalently associated with the 12 kD .beta..sub.2 microglobulin.
The MEC Class I antigen plays an essential role in restriction of the target cell repertoire of cytotoxic T-lymphocytes (CTL). Restriction involves preferential utilization of the different polymorphic MHC Class I antigens, H-2K, -D or -L (for mouse) or HLA-A, -B, or -C (forl human), e.g. in recognition of virally infected cells. For the most part, attention has been directed to the role of the MHC Class I antigens in restricting T-cell activity. However, in addition to restriction of the immune response, Class I MHC antigens may also interact with receptors expressed on the cell surface.
Relevant Literature
For a review of biological functions of MHC Class I antigens see Ohno, Immunol. Rev. (1977) 33:59-69; and Simonsen, Pro. Allergy (1985) 36:151-176. For a description of the insulin receptor see Cuatrecasas, J. Biol. Chem. (1972) 247:1980-1991; Kasuga et al., ibid. (1983) 258:10392-10399; and Kasuga et al., ibid. (1983) 258:10973-10980. For suggestion that Class I antigens and insulin receptors interact, see Olsson, In Cell Fusion: Gene Transfer and Transformation (eds. Beers & Bassett) 395-403 (Raven Press, New York, 1984); Simonsen and Olsson, Ann. Immunol. (1983) 134D:85-92; and Stagsted, et al. Cell (1990) 62:297-307. Other evidence supporting the interaction between MHC products and insulin receptor may be found in Fehlman et al., Phillips et al., ibid. (1986) 83:3474-3478; Due et al., ibid. (1986) 83:6007-6001, and Samson et al., J. Immunology (1986) 137:2293-2298. Evidence for the inhibition of insulin receptor phosphorylation by MHC Class I peptides can be found in Hansen, et al. Proc. Nati. Acad. Sci. USA (1989) 86:3123-3126. Suggestions of a correlation between over-expression of certain Class I products and increased metastatic potential of particular tumors may be found in Wallich et al., Nature (1985) 315:301-305; Katzav et al., Int. J. Cancer (1984) 33:47-415; Olsson, Cancer Rev. (1986) 3:91-114; and Goodenow et al., Science (1985) 230:777-783.
A structural association between epidermal growth factor receptor (EGFR) and MHC Class I on human cells has been suggested by Schreiber et al., J. Cell Biol. (1984) 98:725-731 and Phillips et al., Proc. Nati. Acad. Sci. USA (1986) 83:3474-3478. The effect of MHC Class I peptides on glucose transport mediated by EGFR can be found in Stagsted, et al. J. Biol. Chem. (1993) 268(3):1770-1774. A review of EGFR and its functions may be found in Carpenter and Cohen, Ann. Rev. Biochem. (1979) 48:193-216 and Carpenter, J. Cell Sci. Suppl. (1985) 3:1-9.
Other receptors of interest and appropriate references of relevance to these receptors include: IGF-I, Rosen Science (1987) 237:1452-1458; IGF-II, Simpson and Cushman Ann. Rev. Biochem. (1986) 55:1059-1089; LDL receptor, Hobbs, et al. Human Mutat. (1992) 1:445-466; scavenger LDL receptor, Krieger, et al. J. Biol. Chem. (1993) 268:4569-4572; and .beta..sub.2 -andrenergic receptor, Pitcher, et al. Science (1992) 257:1264-1267.